Solid lipid nanoparticles or microparticles (SLNs or SLMs) or nanospheres are lipid particles having an average diameter smaller than one micron and usually in the range from some hundreds to a few nanometers, which have been thoroughly studied as carriers for controlled drug delivery. SLNs may be prepared by a number of methods from solid lipids, including e.g. high pressure homogenization (EP 605497) and via microemulsions (U.S. Pat. No. 5,250,236).
Reviews of the preparation as well as of the pharmaceutical applications of SLNs are reported for instance in Eur. J. Pharmaceutics and Biopharmaceutics, 50 (2000), 161-177, and in Pharm. Technol. Eur. 13 (2001) 32-42.
Pharmaceutical compositions in form of SLMs suitable for parenteral administration of drugs are particularly disclosed in EP 988031. Said formulations are characterized by specific compounds such as fatty acids, PEG-stearate, dipalmitoylphosphatidylethanolamine-PEG and the like, which stabilize said microparticles avoiding phagocytosis.
Microparticles particularly suited for drug delivery across mucosal tissues and the blood-brain barrier are disclosed in WO 99/27918 and U.S. Pat. No. 6,419,949. A number of medicaments including antibiotics, hormones and antitumor agents of different kinds are specifically cited.
Platinum compounds are among the most effective anticancer drugs used to treat solid tumors. After intravenous administration, platinum species tend to bind irreversibly to plasma proteins (covalent binding) in a time dependent kinetic, with more than 90% drug bound within a few hours from administration. Furthermore, for some new platinum complexes the fraction of drug that is free in plasma water and that is reversibly bound to plasma protein seems to undergo a progressive and rapid degradation to form inactive de-platinated species. These species are likely to be generated because of platinum compound chemical instability in plasma, possibly due to the interaction with nucleophilic thiol-containing endogenous molecules (e.g. cysteine residues, glutathione). The high degree of plasma protein binding in humans probably favors such interaction. Both the high irreversible binding to plasma protein and the fast degradation in human plasma may hamper platinum compounds efficacy in clinical trials.